BARDA`s Role in Combating Antibiotic Resistance

BARDA’S ROLE IN COMBATING
ANTIMICROBIAL RESISTANCE
Joe Larsen, Ph.D.
Deputy Director
BARDA Division of CBRN Medical
Countermeasures
March 2016
Resilient People. Healthy Communities. A Nation Prepared.
BARDA’s Mission
Support advanced development of and make
available medical countermeasures for CBRN
threats, pandemic influenza, and emerging
infectious diseases by transitioning MCM
candidates from early development across the
“Valley of Death“ into advanced development
to regulatory approval
O’Neill Building, Washington, DC
MCM
Development
Pipeline
Core Service
Assistance &
Response
Infrastructure
MCM
Stockpiling
Support the advanced development
of medical countermeasures for
CBRN, pandemic influenza, and
emerging infectious disease threats
Manufacturing
Infrastructure
FDA Approvals
BARDA
Partnerships
Highly Dedicated
and Talented Team
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Development is Expensive, Lengthy and Risky
IND
PHASES
Discovery
Preclinical
Development
NDA/BLA
Phase I
Phase II
Phase III
NIH
DoD
NIH&($11.8B)
Licensure
Production
& Delivery
PBS
$4.3B* ($5.6B)
Project
BioShield
BARDA
ARD ($540M)
$3.1B*
BARDA
PRODUCT PIPELINE
Valley
of
Death
Licensed
Product
Ebola MCMs
2014-2015
MERS-COV MCMs
2012-2015
1-3%
5-17%
10-25%
18-35%
45-70%
90%
PROBABILITY OF SUCCESS TO LICENSURE
TIME
PIPELINE
PHASE COST
3-7 yr
$100M -130M
0.5-2 yr
$60-70M
1-2 yr
$70M-100M
2-3.5 yr
$130M-160M
2.5 -4 yr
1-2 yrs
$190M-220M
$18M-20M
*Represents $1.8B transferred from PBS to support ARD FY09-13, $415M FY14, FY15
* $1.8B transferred to ARD, $255M FY14, FY15
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Products Stockpiled under Project
BioShield
Smallpox
Radiation
Anthrax
Chemical
Botulism
5
Products Stockpiled under Project
BioShield – New in FY 2015
Burn MCMs
Silver Impregnated
Bandages
Enzymatic Debridement
Cell-based Skin Substitutes
6
Autograft-Sparing Technologies
BARDA Supported FDA Approved
Products
Cell-based Influenza Vaccine
Recombinant-based Influenza Vaccine
Novartis
Protein Sciences Corp.
Influenza IV Antiviral Drug
Anthrax Antitoxins
Botulinum
Antitoxin
H1N1 & H5N1 Vaccines w/ Adjuvant
HGS/GSK
Emergent
GlaxoSmithKline
Cangene
Next-Generation
Portable Ventilators
Covidian
Flu/RSV POC
Diagnostic
3M/Focus
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Amgen





Antimicrobial Resistance
Threat
2M infections per year
caused by AMR pathogens
23,000 deaths annually in
US
Estimated economic burden
of $20-35B annually
Categorizes AMR pathogens
in terms of public health
threat: Urgent, Serious, or
Concerning
FQ resistance in E. coli now
greater than 50%,
untreatable GC now
detected in 11 countries.
The Antibiotic Development
Gap
No New Classes to
Treat Gram Negative
Bacilli For 4 Decades
9
The Pipeline is
Insufficient
 504 candidates in Phase 2/3 clinical development
for oncology as of May 2015
 28 antibiotics in Phase 2/3 clinical development
as of March 2015
 7 have predicted efficacy against resistant Gram negative ESKAPE
pathogens
 14 have predicted efficacy against CDC Urgent Threat pathogen
Pew Charitable Trust March 2015
HemOnc today May 2015
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Industry Engagement in New
Antibiotic Development
# of
companies
Over the past 15 years
(1998-2013)
• 14 entries
• 36 exits
• New companies
emerging in 2015,
but we have a lot of
ground to reclaim
Adapted from Rex, JH
Graphic adapted from Kinch MS et al. Drug Discovery
Today, July 2014.
Corporate Entries
Corporate Exits
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The Last Line has Been
Breached
“The emergence of MCR-1 heralds the breach
of the last group of antibiotics, polymyxins, by
plasmid mediated resistance.”
“Although currently confined to China, MCR-1 is
likely to emulate other global resistance
mechanisms, like NDM-1”
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Through the Looking Glass by Lewis Carroll
“Well, in our country," said Alice,
still panting a little, "you'd
generally get to somewhere
else—if you run very fast for a
long time, as we've been
doing."
"A slow sort of country!" said the
Queen. "Now, here, you see, it
takes all the running you can
do, to keep in the same place.
If you want to get somewhere
else, you must run at least
twice as fast as that!"
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The BARDA Model
 The BARDA model works to address market failures
 24 Products FDA approved/cleared for biothreats and
pandemic influenza
 15 Products stockpiled for emergency use
 This model is being successfully applied to antimicrobial
resistance
 Utilization of novel public:private partnerships to
incentivize antibiotic research and development
 4 products in Phase III clinical development
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BARDA Antibacterial Funding Priorities
Drug Class
• Unprecendented
• Novel Target
• Novel Chemistry
• Precedented
• Reduced AR
• Nontraditional
Therapies
• mAbs, phage
• Infection
prevention/interdic
tion
• Vaccines
• Microbiome
Antibiotic Resistance
• C. difficile
• CRE
• N. gonorrhea
• Acinetobacter
• ESBLs
• VRE
• Pseudomonas
• MRSA
• Strep pneumo
• VRSA
• Streptococcus
Biothreat
• B. pseudomallei
• B. mallei
• F. tularensis
• Y. pestis
• B. anthracis
BARDA’s Antimicrobial Portfolio
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BARDA’s Portfolio Partnership for
Antibacterial Drug Development
 Established 5 year $200M public:private partnership in
May 2013
 Utilizes HHS’s first use of Other Transactional Authority
 Supports the development of multiple antibiotic
candidates
 Allows for activities and resources to be adjusted fluidly to
adapt to technical risk and programmatic priorities
 Governance is through a BARDA:GSK Joint Oversight
Committee
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Combating Antibiotic Resistant Bacteria
(CARB)
 In February 2014 OSTP/NSC initiated the President’s
Initiative on Combating Antibiotic Resistant Bacteria
 BARDA was asked to lead the government working
group that developed the National Strategy for
Research and Development of new antimicrobial
therapies
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National Strategy
 GOAL 4: Accelerate Basic and Applied Research and
Development for New Antibiotics, Other Therapeutics,
and Vaccines
Action Plan Metrics
 Within one year:
Status
BARDA will create at least one additional
portfolio partnership with a pharmaceutical or
biotechnology company to accelerate
development of antibacterial drugs.
BARDA and NIH will work to develop a strategy
for establishing the Antibiotic Resistance
Biopharmaceutical Incubator (ARBI).
Economic WG will provide an analysis of
economic incentives and provide
recommendations for implementation
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Program Initiated
Projected Program
Initiation FY16
Recommendations
provided to OSTP in
March 2015
Key Features of the
AZ Partnership
• HHS’s 2nd ever use of Other Transaction Authority
• Partnership will support a portfolio of antibacterial
candidates, the lead of which is aztreonam-avibactam (ATMAVI)
• Strategic decisions will be made by a BARDA-AZ Joint
Oversight Committee
• Fulfills requirement in CARB National Plan that ASPR/BARDA
create at least one additional portfolio partnership with a
pharmaceutical or biotechnology company by March 2016 to
accelerate development of new antibacterial drugs
• Establishes international collaboration between BARDA and
the EU’s Innovative Medicines Initiative (IMI)
• Both entities will provide support for ATM-AVI pivotal
trials
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Incubator
• A robust early stage R&D pipeline of antimicrobial products
is needed to counter the increasing threat of antimicrobial
resistant infections
• There is a need to create an environment to rapidly
develop and commercialize new antimicrobial products
• NIAID and BARDA will collaborate to establish a new
program using a Cooperative Agreement to fund a
Biopharmaceutical Incubator(s) to identify, assemble, and
accelerate a portfolio of innovative early antibacterial
products
• BARDA/NIAID have been conducting market research and
have identified models that currently exist to support the
Incubator concept
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Incubator/Accelerator
Start
UP
Academ
ic Lab
Start
UP
NIH
$
BARDA
Third
Party
Start
UP
BARDA will provide funding
to a third party.
Together, NIH and BARDA
will set strategic goals for
the third party and
monitor progress in
meeting those goals.
Midsize
d
Compa
ny
Academ
ic Lab
Third party could
be a nonprofit,
Evergreen fund,
existing
incubator, etc.
Discovery/Hit to Lead
Phase 1
X
Antibiotic
Candidate
Antibiotic
Candidate
X
Antibiotic
Candidate
X
Antibiotic
Candidate
Antibiotic
Candidate
X
Antibiotic
Candidate
X
Funding will be used to conduct R&D
studies that will advance a candidate drug
in development.
Procurement Sensitive: Not for
Distribution
CARB Accelerator
 Funding Opportunity Announcement was released
on February 17, 2016
 Link to funding announcement: EP-IDS-16-001
 Pre-application workshop is March 3rd at HHH
Building
 Letters of intent are due: March 10th
 Technical Assistance Call: March 18th
 BARDA is anticipating a $30M initial investment
and is projecting up to $250M over the life of
the agreement, pending availability of funds
 BARDA is looking for innovative means to
leverage the Federal investment to increase the
impact of the Accelerator
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Economic Incentives
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BARDA’s Antimicrobial Program
 Summary:
 BARDA’s antimicrobial program will continue to
support the development of novel
antimicrobials and diagnostics to address the
growing public health threat of antimicrobial
resistance and biothreat pathogens
 BARDA will expand our portfolio of partnerships
in FY16
 BARDA is actively conducting outreach to
relevant stakeholders to communicate our
plans to implement the CARB National Strategy
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Thank you!
• www.fedbizopps.gov
─ Official announcements and detailed information
about all government contract solicitations. Open
CBRN BAA:
─ BAA-16-100-SOL-00001
Contact Info: Joe Larsen, Deputy Director BARDA CBRN
Division
Joseph.larsen@hhs.gov 202-260-0050
Technical POC for Research Area #3: Antimicrobial Drugs:
Chris Houchens, Chief, Antibacterial Therapeutics
Christopher.houchens@hhs.gov 202-205-3633
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